Flavoenzymes are proteins that use the flavin co-factor (FAD or FMN) to effect redox transformations and electron transfer. These enzymes function in a variety of essential biological roles, including metabolism, biosynthesis, and electron transport. The diversity of processes catalyzed by these protein is equally impressive, encompassing such divergent transformations such as thiol and amine oxidations, aromatic hydroxylation, and fatty acid dehydrogenation. In previous research, we have used model systems to explore fundamental aspects of flavoenzyme function, in particular the role of enzyme-co-factor interactions in modulating flavin redox processes. These models have allowed us to isolate and quantify specific interactions, and establish their role in determining flavoenzyme function. In our proposed research, we will extend these studies, using a synergistic application of synthetic receptors with chemical, electrochemical, spectroscopic and computational techniques. In chemical studies, we will synthesize receptors to explore the role of recognition processes in the mechanisms and energetics of the biomedically crucial thiol dehydrogenases. Concurrently, we will exploit the ability of electrochemical techniques to directly quantify the energetics of redox processes. In these investigations, we will synthesize receptors to determine the role of "traditional" non-covalent interactions, including hydrogen bonding, in the modulation of flavin redox processes. We will also create receptors to ascertain the role of micro- and macroscopic dipoles on flavin redox processes. These investigations, while focusing on the flavin redox system, will also provide insight into the general issue of the function of electrostatics in enzyme function. Spectroscopically, we will use a two-pronged approach to the study of flavin species. First, we will investigate the effects of recognition on the NMR, EPR and ENDOR spectra of flavins and flavin radicals. We will then use these spectra as calibration for computational methodology. From the synergy of these two methods, we will be able to quantify the effects of individual interactions on fundamental properties, including charge and spin density distributions. Using our model systems as a benchmark, we will also be able to extend with confidence our computational studies to actual enzymatic systems.